Donor liver uridine diphosphate (UDP)-glucuronosyltransferase-1A1 deficiency causing Gilbert's syndrome in liver transplant recipients

Background. Uridine diphosphate-glucuronosyl-transferase-1A1 deficiency, ca using Gilbert's syndrome, has been attributed to two extra (TA) bases in th e TATAA-box of the promoter region of its gene, where the A(TA)(6)TAA allel e corresponds to the normal gene and A(TA)(7)TAA corresponds to a gene with reduced expression. Our aim was to determine whether isolated hyperbilirub inemia in liver transplant recipients was due to Gilbert's syndrome acquire d through the liver allograft, Methods. From 305 patients followed in our Liver Transplant Clinic, five pa tients with isolated unconjugated hyperbilirubinemia in the absence of hemo lysis, recurrent viral hepatitis, and biliary tract pathology were identifi ed; 10 other post-orthotopic liver transplantion patients with normal liver chemistry tests were randomly selected as a control group. DNA was extract ed from paraffin-embedded liver allograft tissue and peripheral lymphocytes and was genotyped for the TA repeat at the uridine diphosphate glucononosy ltransferase-1A1 promoter region by polymerase chain reaction and acrylamid e gel electrophoresis, Homozygosity for the (TA), allele was considered dia gnostic of Gilbert's syndrome. Results. The mean serum total bilirubin level of the study patients was 2.2 8 mg/dl (range 1,8-3,0), consisting predominantly of the unconjugated form; that of the control patients was 0.76 mg/dl (range 0,4-1,1), The liver tis sue from all five patients in the study group possessed the homozygous A(TA )(7)TAA genotype that was not observed in their lymphocytes, None of the li ver tissue from the control patients demonstrated homozygosity for the A(TA )(7)TAA allele, Conclusion. Uridine diphosphate-glucuronosyltransferase-1A1 deficiency, cau sing Gilbert's syndrome, may be carried by the donor liver and present with isolated unconjugated hyperbilirubinemia in liver transplant recipients.